Search Results (1,695)

Non-small cell lung cancer (NSCLC) is a predominant form of lung cancer that is often diagnosed at an advanced metastatic stage. The processes of cancer cell migration and invasion involve epithelial-to-mesenchymal transition (EMT), which is crucial for metastasis. Targeting cancer aggressiveness with effective plant compounds has gained attention as a potential adjuvant therapy. Eurycomanone (ECN), a bioactive quassinoid found in the root of Eurycoma longifolia Jack, has demonstrated anti-cancer activity against various carcinoma cell lines, including human NSCLC cells. This study aimed to investigate the in vitro effects of ECN on the migration and invasion of human NSCLC cells and to elucidate the mechanisms by which ECN modulates the EMT in these cells. Non-toxic doses (≤IC20) of ECN were determined using the MTT assay on two human NSCLC cell lines: A549 and Calu-1. The results from wound healing and transwell migration assays indicated that ECN significantly suppressed the migration of both TGF-β1-induced A549 and Calu-1 cells. ECN exhibited a strong anti-invasive effect, as its non-toxic doses significantly suppressed the TGF-β1-induced invasion of NSCLC cells through Matrigel and decreased the secretion of MMP-2 from these cancer cells. Furthermore, ECN could affect the TGF-β1-induced EMT process in various ways in NSCLC cells. In TGF-β1-induced A549 cells, ECN significantly restored the expression of E-cadherin by inhibiting the Akt signaling pathway. Conversely, in Calu-1, ECN reduced the aggressive phenotype by decreasing the expression of the mesenchymal protein N-cadherin and inhibiting the TGF-β1/Smad pathway. In conclusion, this study demonstrated the anti-invasive activity of eurycomanone from E. longifolia Jack in human NSCLC cells and provided insights into its mechanism of action by suppressing the effects of TGF-β1 signaling on the EMT program. These findings offer scientific evidence to support the potential of ECN as an alternative therapy for metastatic NSCLC. Full article

Snail and Zeb1 have been suggested as markers for the hybrid/mixed epithelial (E)/mesenchymal (M) state of cancer cells. Such cancer cells co-express E- and M-specific transcripts and possess cancer stem cell properties. M13HS-2/-8 tumor hybrid clones derived from human M13SV1-EGFP-Neo breast epithelial cells and human HS578T-Hyg breast cancer cells exhibited co-expression of Snail and Zeb1. To explore the impact of Snail on stemness/epithelial-to-mesenchymal transition (EMT)-related properties in M13HS-2/-8 tumor hybrid clones, Snail was knocked out (KO) using CRISPR/Cas9. Mammosphere formation, colony formation, Western blot analyses, cell migration, and invasion assays were conducted for the characterization of Snail knockout cells. Interestingly, Snail-KO in M13SV1-EGFP-Neo cells resulted in the up-regulation of vimentin and N-cadherin, suggesting EMT induction, which was associated with a significantly enhanced colony formation capacity. In contrast, EMT marker pattern and colony formation capacities of M13HS-2/-8 Snail-KO tumor hybrid clones remained unchanged. Notably, the mammosphere formation capacities of M13HS-2/-8 Snail-KO tumor hybrid clones were significantly reduced. The migratory behavior of all Snail-KO cells was not altered compared with their wild-type counterparts. In contrast, M13HS-2 hybrids and their M13HS-2 Snail-KO variant exhibited a markedly enhanced invasive capacity. Therefore, Snail plays a role as a mediator of stemness properties rather than mediating EMT. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disorder characterized by excessive scarring of lung tissue, predominantly affecting middle-aged and elderly populations. Oxidative stress plays a pivotal role in the pathogenesis of pulmonary fibrosis, disrupting redox homeostasis and driving fibrotic progression. Glutathione reductase (GSR), a key antioxidant enzyme, is essential for maintaining cellular glutathione (GSH) levels and mitigating oxidative damage. However, the specific involvement of GSR in IPF remains poorly understood. This study found that GSR levels were downregulated in IPF patients and mice treated with bleomycin (BLM). GSR knockdown enhanced epithelial-to-mesenchymal transition (EMT) in A549 cells and promoted the activation of MRC5 cells. Additionally, GSR depletion promoted cellular migration and senescence in both A549 and MRC5 cells. Mechanistically, silencing GSR in A549 and MRC5 cells led to a marked reduction in intracellular GSH levels, resulting in elevated reactive oxygen species (ROS) accumulation, thereby promoting the activation of the TGF-β/Smad2 signaling pathway. In conclusion, our findings demonstrate that GSR deficiency aggravates pulmonary fibrosis by impairing antioxidant defense mechanisms, promoting EMT, and activating fibroblasts through the TGF-β/Smad2 signaling. These findings suggest that GSR may be essential in reducing the fibrotic progression of IPF. Full article

To improve implant osseointegration while preventing infection, we developed a strontium (Sr)-doped Ti₃C₂T_x MXene coating on titanium, aiming to synergistically enhance bone integration and antibacterial performance. MXene is a family of two-dimensional transition-metal carbides/nitrides whose abundant surface terminations endow high hydrophilicity and bioactivity. The coating was fabricated via anodic electrophoretic deposition (40 V, 2 min) of Ti₃C₂T_x nanosheets, followed by SrCl₂ immersion to incorporate Sr²⁺. The coating morphology, phase composition, chemistry, hydrophilicity, mechanical stability, and Sr²⁺ release were characterized. In vitro bioactivity was assessed with rat bone marrow mesenchymal stem cells (BMSCs)—with respect to viability, proliferation, migration, alkaline phosphatase (ALP) staining, and Alizarin Red S mineralization—while the antibacterial efficacy was evaluated against Staphylococcus aureus (S. aureus) via live/dead staining, colony-forming-unit enumeration, and AlamarBlue assays. The Sr-doped MXene coating formed a uniform lamellar structure, lowered the water-contact angle to ~69°, and sustained Sr²⁺ release (0.36–1.37 ppm). Compared to undoped MXene, MXene/Sr enhanced BMSC proliferation on day 5, migration by 51%, ALP activity and mineralization by 47%, and reduced S. aureus viability by 49% within 24 h. Greater BMSCs activity accelerates early bone integration, whereas rapid bacterial suppression mitigates peri-implant infection—two critical requirements for implant success. Sr-doped Ti₃C₂T_x MXene thus offers a simple, dual-function surface-engineering strategy for dental and orthopedic implants. Full article

Atherosclerosis constitutes a pathological process underlying cardiovascular diseases. There is growing evidence that IGFBP5 is a causative factor, although the conclusions of different studies are inconsistent. The present study aims to confirm the role and mechanism of IGFBP5 in atherosclerosis. The expression of IGFBP5 was induced in the skeletal muscle of male ApoE^−/− mice, an atherosclerosis model, using adeno-associated virus, resulting in elevated circulating IGFBP5 levels. Changes in blood lipids were detected, and pathological changes in the aorta were observed. Analysis of IGFBP5 function using RNA sequencing and validation were performed in a mouse aortic smooth muscle cell line. The results demonstrated that IGFBP5 overexpression exacerbated the development of aortic lesions in this murine models without any discernible alterations in lipid profile parameters; the arterial transcriptomic landscape revealed that heightened IGFBP5 levels predominantly influenced pathways governing smooth muscle cell proliferation and motility. In vitro experimentation corroborated these findings, showcasing the stimulatory effect of IGFBP5 on VSMC (vascular smooth muscle cell) proliferation and migration, provoking a transition toward a proliferative phenotype. IGFBP5 promotes atherosclerosis in ApoE^−/− mice through the phenotypic transformation of VSMCs. This finding suggests that IGFBP5 has the potential to serve as an indicator of atherosclerosis diagnosis and a target for therapeutic interventions in the future. Full article

Given the increasing challenges posed by frequent extreme climatic events, understanding the climate–human connection between the climate system and the transitions of ancient civilizations is crucial for addressing future climatic challenges, especially when examining the relationship between the abrupt events of the Holocene and the Neolithic culture development. Compared with the globally recognized “4.2 ka collapse” of ancient cultures, the initial start time and the cultural significance of the 5.5 ka climatic fluctuation are more complex and ambiguous. The Hongshan culture (6.5–5.0 ka) is characterized by a complicated society evident in its grand public architecture and elaborate high-status tombs. However, the driving mechanisms behind cultural changes remain complex and subject to ongoing debate. This paper delves into the role of climatic change in Hongshan cultural shifts, presenting an integrated dataset that combines climatic proxy records with archaeological data from the Hongshan culture period. Based on synthesized aeolian, fluvial-lacustrine, loess, and stalagmite deposits, the study indicates a relatively cold and dry climatic fluctuation occurred during ~6.0–5.5 ka, which is widespread in the Horqin dune field and adjacent areas. Combining spatial analysis with ArcGis 10.8 on archaeological sites, we propose that the climatic fluctuation between ~6.0–5.5 ka likely triggered the migration of the Hongshan settlements and adjustment of survival strategies. Full article

The accurate mapping of crop planting patterns is vital for sustainable agriculture and food security, particularly in regions with complex cropping systems and limited cloud-free observations. This research focuses on the Jianghan Plain in southern China, where diverse planting structures and persistent cloud cover make consistent monitoring challenging. We integrated multi-temporal Sentinel-2 and Landsat-8 imagery from 2017 to 2021 on the Google Earth Engine platform and applied a sample migration strategy to construct multi-year training data. A random forest classifier was used to identify nine major planting patterns at a 10 m resolution. The classification achieved an average overall accuracy of 88.3%, with annual Kappa coefficients ranging from 0.81 to 0.88. A spatial analysis revealed that single rice was the dominant pattern, covering more than 60% of the area. Temporal variations in cropping patterns were categorized into four frequency levels (0, 1, 2, and 3 changes), with more dynamic transitions concentrated in the central-western and northern subregions. A multiscale geographically weighted regression (MGWR) model revealed that economic and production-related factors had strong positive associations with crop planting patterns, while natural factors showed relatively weaker explanatory power. This research presents a scalable method for mapping fine-resolution crop patterns in complex agroecosystems, providing quantitative support for regional land-use optimization and the development of agricultural policies. Full article

Background: The mechanisms underlying the metastasis of non-small-cell lung cancer (NSCLC) have long been a focal point of medical research. The anti-tumor effects of chelerythrine (CHE) have been confirmed; however, its ability to inhibit tumor metastasis and the underlying mechanisms remain unknown. The aim of this study was to investigate the inhibitory effects and molecular mechanisms of CHE on transforming growth factor-beta (TGF-β)-induced epithelial–mesenchymal transition (EMT). Methods: Wound healing and Transwell assays were employed to evaluate TGF-β-induced migration in A549 cells and the inhibitory effects of CHE. Ribonucleotide reductase subunit M2 (RRM2) expression levels were detected via Western blot and immunofluorescence staining. Western blot and RT-qPCR were used to examine the expression levels of EMT-related markers. Animal experiments were conducted to analyze the role of RRM2 in the CHE inhibition of TGF-β-induced lung cancer metastasis. Results: This study found that TGF-β treatment enhanced the metastasis of A549 cells, while CHE inhibited the expression of TGF-β-induced EMT-related transcription factors by RRM2, thereby suppressing tumor cell migration (p < 0.05). Furthermore, the oral administration of CHE inhibited the metastasis of A549 cells to the lungs from the tail vein in mice, consistent with in vitro findings. Despite the high doses of CHE used, there was no evidence of toxicity. Conclusions: Our data reveal the mechanism of the anti-metastatic effects of CHE on TGF-β-induced EMT and indicate that CHE can be used as an effective anti-tumor treatment. Full article

Fuchs endothelial corneal dystrophy (FECD) is a progressive corneal disease characterized by corneal endothelial cell (CEC) loss and guttae formation. Elevated levels of Transforming Growth Factor-Beta 1 and 2 (TGF-β1/-β2) have been reported in the aqueous humor (AH) of FECD patients and have been implicated with abnormal extracellular matrix (ECM) production, endothelial-to-mesenchymal transition (EndoMT), the unfolded protein response, and cell death. However, how TGF-β signaling affects cell migration in FECD remains to be elucidated. In this study, we found that TGF-β2 levels were significantly elevated in the AH of FECD patients compared to controls. We performed bulk RNA sequencing on FECD CECs treated with TGF-β1 or TGF-β2 and identified the epithelial-to-mesenchymal (EMT) pathway as one of the top dysregulated pathways. We found that TGF-β1 and TGF-β2 increased EMT markers, filamentous-actin (F-actin) expression and produced more EMT-like phenotype in FECD and control CECs. We also observed that TGF-β1 and TGF-β2 significantly increased FECD CEC migration speed as detected by scratch assay and individual cell tracking and promoted individual cellular migration behavior. This study provides novel insight into FECD pathogenesis and how increased TGF-β signaling promotes EndoMT and alters cellular migration in FECD CECs. Full article

Rapid urbanization in China has driven substantial rural population out-migration, raising concerns about its implications for the governance of land commons in villages. While existing studies have acknowledged the effects of migration on rural resource management, little attention has been paid to its influence on the self-governance of rural public open spaces (POSs). This study adopts the social–ecological systems (SES) framework to examine how rural out-migration shapes POS self-governance mechanisms. Based on survey data from 594 villagers across 198 villages in Taigu District, partial least squares structural equation modeling (PLS-SEM) and a mediation model grounded in the SES framework were employed for analysis. The results indicate that rural out-migration does not exert a direct impact on POS self-governance. Instead, it negatively influences governance outcomes through full mediation by villager organizations, the left-behind population, collective investment in POSs, and self-organizing activities. Notably, the mediating roles of the left-behind population and self-organizing activities account for 67.38% of the total effect, underscoring their critical importance. Drawing on these insights, the study proposes four policy recommendations to strengthen rural POS self-governance under conditions of demographic transition. This research contributes to the literature by being the first to incorporate an external social factor—rural out-migration—within the SES framework in the context of POS governance, thereby advancing both theoretical and practical understandings of rural commons management. Full article

Background/Objectives: Fish eggs activated with UV-irradiated spermatozoa and exposed to the High Hydrostatic Pressure (HHP) shock to inhibit first cell cleavage develop as gynogenetic Doubled Haploids (DHs) that are fully homozygous individuals. Due to the expression of the recessive genes and side effects of the gamete treatment, survival of fish DHs is rather low, and most of the mitotic gynogenotes die before hatching. Nevertheless, as maternal gene products provided during oogenesis control the initial steps of embryonic development in fish, a maternal effect on the survival of gynogenotes needs to be also considered to affect efficiency of gynogenesis. Thus, the objective of this research was to apply an RNA-seq approach to discriminate transcriptional differences between rainbow trout (Oncorhynchus mykiss) eggs with varied abilities to develop after gynogenetic activation. Methods: Gynogenetic development of rainbow trout was induced in eggs originated from eight females. Maternal RNA was isolated and sequenced using RNA-Seq approach. Survival rates of gynogenotes and transcriptome profiles of eggs from different females were compared. Results: RNA-seq analysis revealed substantial transcriptional differences between eggs originated from different females, and a significant correlation between the ability of the eggs for gynogenesis and their transcriptomic profiles was observed. Genes whose expression was altered in eggs with the increased survival of DHs were mostly associated (GO BP) with the following biological processes: development, cell differentiation, cell migration and protein transport. Some of the genes are involved in the oocyte maturation (RASL11b), apoptosis (CASPASE 6, PGAM5) and early embryogenesis, including maternal to zygotic transition (GATA2). Conclusions: Inter-individual variation of the transcription of maternal genes correlated with the competence of eggs for gynogenesis suggest that at least part of the mortality of the rainbow trout DHs appear before activation of zygotic genome and expression of the lethal recessive traits. Full article

The paper presents the geochemical characteristics of 26 selected oil seeps, more than half of which are remnants of old oil wells. The samples were collected from three tectonic units: the Magura, Silesian, and Skole units in the Polish part of the Carpathians. The analyzed seeps are mainly located on outcrops of Inoceramian beds within the Magura nappe, the Krosno Beds and Transition Beds in the Silesian nappe, as well as the Menilite Beds of the Skole unit. The study primarily focused on genetic characteristics, which were used to correlate the seeps with the oils from the deposits of these tectonic units and to assess the degree of secondary alterations. All hydrocarbon seeps were analyzed in terms of their location on surface cross-sections, and attempts were made to assign them features based on the classification proposed in 1952, which takes into account the tectonic characteristics of the regions where the seeps were identified. In the general genetic characterization, these seeps did not show significant differences, suggesting a similar source of supply as the crude oils. Among the analyzed seeps, three genetic groups were distinguished. For correlation purposes, information from published materials on crude oils and their genetic characteristics was used. Of the five classification types described in the literature, only two could be assigned to those occurring in the Carpathians. Considering the tectonic structure and the location of the seeps (based on surface cross-sections), it has been determined that most of the analyzed seeps are the result of migration along faults connecting source rocks or, less frequently, deformed deep accumulations with the surface. Full article

Building upon the geological cycle theory, this study proposes fault cycles as a critical component of tectonic cyclicity in petroliferous basins. Focusing on reservoir-controlling faults in the southwestern Qaidam Basin, we systematically analyze fault architectures and identify three distinct fault activation episodes: the Lulehe Formation (LLH Fm.), the upper part of the Xiaganchaigou Formation (UXG Fm.), and the Shizigou Formation (SZG Fm.). Three types of fault cycle models are established. These fault cycles correlate with the evolution of regional tectonic stress fields, corresponding to the Cenozoic transition from extensional to compressional stress regimes in the basin. Mechanistic analysis reveals the hierarchical control of fault cycles in hydrocarbon systems: the early cycle governs the proto-basin geometry and low-amplitude structural trap development; the middle cycle affects the source rock distribution; and the late cycle controls trap finalization and hydrocarbon migration. This study proposes a fault cycle-controlled accumulation model, providing a dynamic perspective that shifts from conventional static fault concepts to reveal fault activity periodicity and its critical multi-phase control over hydrocarbon migration and accumulation, essential for exploration in multi-episodic fault provinces. Full article

The relict tree Cercidiphyllum japonicum, a Tertiary paleoendemic with significant ecological and timber value, prefers warm–cool humid climates and acidic soils. Using MaxEnt and ArcGIS, we modeled its distribution under current and future climate scenarios (SSP, Shared Socioeconomic Pathways). High-suitability areas (>0.6 probability) under current conditions are mainly concentrated in the Sichuan Basin and the Yellow–Yangtze transition zones. By 2050, projections show northwestward expansions (14.32–18.76% increase in area) and eastward movement toward Central China under both SSP1-2.6 and SSP5-8.5 scenarios. However, by 2090, habitat loss could exceed 22% under SSP5-8.5. The main environmental drivers of its distribution are minimum coldest-month temperature (bio6, 38.7%), annual precipitation (bio12, 29.1%), and temperature range (bio7, 18.5%). Precipitation seasonality and thermal extremes are expected to become more significant constraints in the future. Conservation strategies should focus on the following: (1) protecting refugia in the Daba–Wushan mountains, (2) facilitating assisted migration to northwestern high-latitude regions, and (3) preserving microclimates. This study offers a framework for evidence-based conservation of paleoendemic species under climate change. Full article

Using the combination of Concentrated solar power (CSP) and calcium looping (CaL) technology is an effective way to solve the problems of intermittent solar energy, but calcium-based materials are prone to sintering due to the densification of the surface structure during high-temperature cycling. In this study, the enhancement mechanism of Co and Cr doping in terms of the adsorption properties of CaO was investigated by Density Functional Theory (DFT) calculations. The results indicate that Co and Cr doping shortens the bond length between metal and oxygen atoms, enhances covalent bonding interactions, and reduces the oxygen vacancy formation energy. Meanwhile, the O²⁻ diffusion energy barrier decreased from 4.606 eV for CaO to 3.648 eV for Co-CaO and 2.854 eV for Cr-CaO, which promoted CO₂ adsorption kinetics. The CO₂ adsorption energy was significantly increased in terms of the absolute value, and a partial density of states (PDOS) analysis indicated that doping enhanced the C-O orbital hybridization strength. In addition, Ca₄O₄ cluster adsorption calculations indicated that the formation of stronger metal–oxygen bonds on the doped surface effectively inhibited particle migration and sintering. This work reveals the mechanisms of transition metal doping in optimizing the electronic structure of CaO and enhancing CO₂ adsorption performance and sintering resistance, which provides a theoretical basis for the design of efficient calcium-based sorbents. Full article